Recently, there has been an outbreak of atypical pneumonia in Guangdong province in mainland China. Between November 2002 and March 2003, there were 792 reported cases with 31 fatalities (WHO. Severe Acute Respiratory Syndrome (SARS) Weekly Epidemiol Rec. 2003; 78: 86). In response to this crisis, the Hospital Authority in Hong Kong has increased the surveillance on patients with severe atypical pneumonia. In the course of this investigation, a number of clusters of health care workers with the disease were identified. In addition, there were clusters of pneumonia incidents among persons in close contact with those infected. The disease was unusual in its severity and its progression in spite of the antibiotic treatment typical for the bacterial pathogens that are known to be commonly associated with atypical pneumonia. The disease was given the acronym Severe Acute Respiratory Syndrome (“SARS”).
A novel coronavirus associated with SARS (herein interchangeably referred to “SCoV”, “CoV” or “hSARS” virus) has been identified as the etiologic agent of SARS (Ksiazek, T G, et al. A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N. Engl. J. Med. 2003; published online (10.1056/NEJMMoa030781); Marra, M A, et al. The Genome Sequence of the SARS-Associated Coronavirus. Science 2003; published online (10.1126/science. 1085953); Peiris, J S, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003; 361: 1319–1325; Drosten, C, et al. Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome. N Engl J Med. 2003; published online (10.1056/NEJMoa030747); and Rota, P A, et al. Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. Science 2003; (10.1126/science. 1085952)). The complete genome sequences of coronavirus strains isolated from different patients in various geographic locations were reported recently (Marra et al., supra.; Rota et al., supra.; and U.S. patent application Ser. No. 60/464,886, filed Apr. 23, 2003, and Ser. No. 10/808,121 filed Mar. 24, 2004; each of which is incorporated herein by reference in its entirety). The isolated virus is an enveloped, single-stranded RNA virus of positive polarity which belongs to the order, Nidovirales, of the family, Coronaviridae. The total genome of the SARS coronavirus is 29,727 nucleotides in length (see, for example, Genbank NCBI Accession Nos:AY274119, AY304495 and AY278491). This is the largest genome yet found in any of the known RNA viruses. The genome organization of the hSARS virus is similar to that of other coronaviruses. It encodes for at least 5 gene products, i.e., replicase, spike glycoprotein (S), membrane protein (M), envelope protein (E) and nucleocapsid protein (N), with eleven possible open reading frames (see FIGS. 1A and 4A). The exact numbers of gene products are not clear yet. Currently, there is no known effective treatment for SARS. Accordingly, drug development for the treatment of SARS is urgently needed. The inventors have formulated RNAi molecules useful for inhibiting the infection and replication of the hSARS virus. This offers the possibility of developing a new anti-viral therapy for SARS.